Lu Liu, Yao Qing-Yu, Ruan Sha-Sha, Hu Jia-Wei, Long Wen-Jun, Dai Wen-Zhuo, Ma Tao, Zhu Xi-Chen
Department of Neurology, The Affiliated WuXi NO.2 People's Hospital of Nanjing Medical University.
Department of Neurology, The WuXi NO.2 People's Hospital, Affiliated Wuxi Clinical College of Nantong University, Wuxi, Jiangsu, China.
Psychiatr Genet. 2021 Dec 1;31(6):216-229. doi: 10.1097/YPG.0000000000000291.
Complement component (3b/4b) receptor 1 (CR1) is an interesting candidate gene which has a close connection with Alzheimer's disease, and its polymorphisms have been reported to link to the late-onset Alzheimer's disease (LOAD) susceptibility. However, the findings of these related studies are inconsistent. Objective To explore the effect of CR1 genetic variants in LOAD susceptibility. MethodsWe searched relevant studies for the period up to 1 November 2020. And odds ratios (ORs) and their 95% confidence intervals (CIs) were utilized to assess the strength of the association. In addition, we carried out a case-control association study to assess their genetic association.
Finally, a total of 30 articles with 30108 LOAD cases and 37895 controls were included. Significant allele frequency between LOAD patients and controls was observed in rs3818361 and rs6656401 (rs3818361, T vs. C: OR,1.18; 95% CI, 1.13-1.23; rs6656401, A vs. G: OR, 1.23; 95% CI, 1.10-1.36). Moreover, these results remain significant in subgroup of rs3818361 in Asia or America (OR,1.26; 95% CI,1.06-1.45; OR, 1.18; 95% CI, 1.13-1.24, respectively) and rs6656401 in Europe (OR = 1.26; 95% CI, 1.09-1.42). In addition, the two single nucleotide polymorphisms were proved to significantly increase LOAD risk in the overall population under the dominant model (OR = 1.12; 95% CI, 1.02-1.21; OR = 1.18, 95% CI, 1.15-1.22, respectively). Our case-control study showed that the distribution of rs6656401 genotype was significant (P = 0.000; OR, 6.889; 95% CI, 2.709-17.520), suggesting the A allele of rs6656401 is the risk allele.
These available data indicate that rs6656401 in CR1 is significant to increase LOAD risk.
补体成分（3b/4b）受体1（CR1）是一个与阿尔茨海默病密切相关的有趣候选基因，其多态性已被报道与晚发性阿尔茨海默病（LOAD）易感性相关。然而，这些相关研究的结果并不一致。目的：探讨CR1基因变异对LOAD易感性的影响。方法：检索截至2020年11月1日的相关研究。采用优势比（OR）及其95%置信区间（CI）评估关联强度。此外，我们进行了一项病例对照关联研究以评估它们的遗传关联性。
最终，共纳入30篇文章，涉及30108例LOAD病例和37895例对照。在rs3818361和rs6656401中观察到LOAD患者与对照之间的显著等位基因频率（rs3818361，T与C：OR，1.18；95%CI，1.13 - 1.23；rs6656401，A与G：OR，1.23；95%CI，1.10 - 1.36）。此外，这些结果在rs3818361亚洲或美洲亚组（分别为OR，1.26；95%CI，1.06 - 1.45；OR，1.18；95%CI，1.13 - 1.24）和rs6656401欧洲亚组（OR = 1.26；95%CI，1.09 - 1.42）中仍然显著。此外，在显性模型下，这两个单核苷酸多态性被证明在总体人群中显著增加LOAD风险（分别为OR = 1.12；95%CI，1.02 - 1.21；OR = 1.18，95%CI，1.15 - 1.22）。我们的病例对照研究表明rs6656401基因型的分布具有显著性（P = 0.000；OR，6.889；95%CI，2.709 - 17.520），表明rs6656401的A等位基因是风险等位基因。
这些现有数据表明CR1中的rs6656401对增加LOAD风险具有显著性。
